The proposed research program will involve integrated collaborative studies of the epidemiology, biology and natural history of hepatitis C virus (HCV) infections in Northern Thailand. Infections with HCV are a worldwide health problem and are a major cause of chronic liver disease, liver cancer and cirrhosis. It is estimated that 4 million persons in the United States and 180 million persons worldwide are infected with HCV. After infection 80 percent of individuals will become chronic carriers and 20 percent of them will progress to chronic liver disease or cancer in the next 15-20 years. Epidemiologic studies in some populations have found high rates of HCV in injection drug users and lower but elevated rates from sexual and perinatal transmission. However, infections in many individuals are cryptogenic. The reasons for the persistence of HCV infection in such a high proportion of infected individuals is not clear. However, the virus is genetically quite diverse and viral variation with the emergence of new quasispecies usually occurs in chronically infected people. Furthermore the epidemiology and transmission of HCV is intertwined with HIV, so many persons who are infected with both viruses may be immunosuppressed. The studies we have planned will involve comprehensive investigations of the epidemiology, virology and natural history of HCV infections in various populations in Northern Thailand, most of whom are being evaluated for HIV infection. Liver cancer is one of the leading causes of cancer in Thailand and HCV prevalence in blood donors is 8-10 fold greater than in the U.S. The study populations will include injection drug users, sex workers, STD patients, military recruits, blood donors and their spouses and general community populations. Through the transfer of technology for HCV research to our collaborators, we hope to focus on understanding the biology and epidemiology of HCV and the development of more effective prevention of HCV.